All Gram negative bacteria studied to date are known to be able to produce outer membrane vesicles (OMVs) (Kulp A, Kuehn M J. Biological functions and biogenesis of secreted bacterial outer membrane vesicles. Annu Rev Microbiol; 64:163-84). Due to their immunogenic properties, self-adjuvanticity, ability to be taken up by mammalian cells, and capacity for enhancement by recombinant engineering, OMVs are attractive candidates for vaccine delivery platforms. The use of an OMV as a vaccine is exemplified by the MeNZB vaccine, which has been effectively and safely used against bacterial meningitis in New Zealand, leading to a drastic reduction in the incidence of this type of infection in the country (Arnold R, Galloway Y, McNicholas A, O'Hallahan J. Effectiveness of a vaccination programme for an epidemic of meningococcal B in New Zealand. Vaccine; 29(40):7100-6). OMVs have also been safely used in human vaccines used in Cuba, Brazil and Norway, among other countries. Several studies reported that OMV vaccines can protect mice from infection by Bordetella pertussis, Salmonella typhimurium and Brucella melitensis, among other pathogens (Asensio C J, Gaillard M E, Moreno G, Bottero D, Zurita E, Rumbo M, et al. Outer membrane vesicles obtained from Bordetella pertussis Tohama expressing the lipid A deacylase PagL as a novel acellular vaccine candidate. Vaccine 2011; 29(8):1649-56). It is generally believed that protection is due to the immunogenicity of certain outer membrane proteins found on the OMVs.
OMVs are mainly composed of lipopolysaccharide (LPS), outer membrane and periplasmic proteins and phospholipids, and are formed by blebbing of the outer membrane. LPS contains lipid A, also known as endotoxin, and generally, O antigen, which is a polysaccharide of variable structure. Previous efforts to engineer OMV were directed to manipulation of the protein content in OMV preparations (Chen D J, Osterrieder N, Metzger S M, Buckles E, Doody A M, DeLisa M P, et al. Delivery of foreign antigens by engineered outer membrane vesicle vaccines. Proc Natl Acad Sci USA 2010;107(7):3099-104; Kim J Y, Doody A M, Chen D J, Cremona G H, Shuler M L, Putnam D, et al. Engineered bacterial outer membrane vesicles with enhanced functionality. J Mol Biol 2008;380(1):51-66; Koeberling O, Giuntini S, Seubert A, Granoff DM. Meningococcal outer membrane vesicle vaccines derived from mutant strains engineered to express factor H binding proteins from antigenic variant groups 1 and 2. Clin Vaccine Immunol 2009;16(2):156-62; and van de Waterbeemd B, Streefland M, van der Ley P, Zomer B, van Dijken H, Martens D, et al. Improved OMV vaccine against Neisseria meningitidis using genetically engineered strains and a detergent-free purification process. Vaccine 2010;28(30):4810-6). Furthermore, work on engineering strains to produce OMV containing modified, less toxic, lipid A has been published (Asensio C J, Gaillard M E, Moreno G, Bottero D, Zurita E, Rumbo M, et al. Outer membrane vesicles obtained from Bordetella pertussis Tohama expressing the lipid A deacylase PagL as a novel acellular vaccine candidate. Vaccine 2011;29(8):1649-56 and Koeberling O, Seubert A, Granoff D M. Bactericidal antibody responses elicited by a meningococcal outer membrane vesicle vaccine with overexpressed factor H-binding protein and genetically attenuated endotoxin. J Infect Dis 2008;198(2):262-70).
Current vaccines against Gram positive bacteria, like Streptococcus pneumoniae, consist of chemically prepared conjugates comprising capsular polysaccharide chemically coupled to a protein carrier. Gram positive bacteria do not produce OMVs.
There remains a need for alternative OMV vaccines and OMV vaccines against Gram positive bacteria.
This background information is provided for the purpose of making known information believed by the applicant to be of possible relevance to the present invention. No admission is necessarily intended, nor should be construed, that any of the preceding information constitutes prior art against the present invention.